New treatment may work with folic acid to prevent neural tube defects like spina bifida

12 August 2013

Researchers at the UCL Institute of Child
Health (ICH) are investigating a new treatment that could work alongside
folic acid to boost its effectiveness and prevent a greater proportion
of neural tube defects – such as spina bifida – in early pregnancy.

A new study published in the journal Brain shows
that the new treatment, when tested in mice, reduced the incidence of
neural tube defects (NTDs) by 85 per cent. This new approach was also
successful in preventing some kinds of NTDs that are currently
unresponsive to folic acid.

Researchers at the ICH, which is the
research partner of Great Ormond Street Hospital for Children NHS
Foundation Trust, believe the findings could make way for future trials
in patients, to investigate whether the same level of prevention can be
achieved for human NTDs.

NTDs such as spina bifida and
anencephaly are still among the most common birth defects worldwide,
affecting about 1 in 1,000 pregnancies with much higher rates in some
countries.

Folic acid supplements taken in the very early stages
of human pregnancy, when an embryo’s central nervous system is still
developing, currently prevent a proportion of NTDs (20-80 per cent
depending on geographic region). Folic acid works by helping the
embryo’s neural tube to close normally, which is an essential step of
development (failure of this process results in NTDs). However, a
significant number of NTDs are unresponsive to folic acid supplements.

This nucleotide treatment could boost the effects of folic acid and offer expectant mothers an even more reliable safeguard against relatively common defects like spina bifida.

Professor Nicholas Green, Institute of Child Health

One
reason why folic acid might not always be effective is that a ‘genetic
blockage’ can occur in the way folic acid is handled, or metabolised, in
cells. In such cases, even if folic acid is taken early in pregnancy it
is blocked from having the desired effect on the embryo. The new
treatment being tested at the ICH involves supplementing with
‘nucleotides’, which are needed to make DNA as cells divide in the
growing embryo. Nucleotides can bypass the blockage in the way folic
acid is handled, ensuring the growth of crucial cells in the embryo.

NTDs
are likely to have many possible causes and the ICH team considers that
the most effective way to reduce the risk of NTDs is to use a
combination of different treatments. In previous studies they found that
a particular vitamin, inositol, has a protective effect and this is
being tested in a clinical trial.

Similar studies are now
proposed for the ‘nucleotide’ treatment, and researchers envisage that a
single tablet could eventually be developed for women planning a baby,
which would contain folic acid and the new protective compounds.

Commenting
on the new research, Nicholas Greene, Professor of Developmental
Neurobiology at the ICH, said: “We are still in the early stages of this
research, but we hope that these promising results in mice can
eventually be replicated with human NTDs. If it is found to be
effective, this nucleotide treatment could boost the effects of folic
acid and offer expectant mothers an even more reliable safeguard against
relatively common defects like spina bifida.”

Professor Greene added:
“While we continue our research into this new treatment, it’s important
to emphasise that folic acid supplements remain the most effective
prevention against NTDs currently available for women who are planning a
baby. While we are greatly encouraged by these new findings, I would
strongly urge women to continue taking folic acid in its current form
until we reach a point where additional supplements might become
available.”

The new research has been funded by the Wellcome
Trust, Medical Research Council and Newlife Foundation for Disabled
Children, who also co-sponsored the establishment of the Newlife Birth
Defects Research Centre at the UCL Institute of Child Health.